Corticosteroid-binding globulin: a possible early predictor of infection in acute necrotizing pancreatitis

OBJECTIVE: Infected pancreatic necrosis is the main cause of death in patients with acute pancreatitis, and therefore its early prediction is of utmost importance. Endogenous cortisol metabolism plays a basic role both in the course of acute pancreatitis and in the process of infection. The purpose of this study was to analyze corticosteroid-binding globulin (CBG), total cortisol, calculated free cortisol and adrenocorticotropic hormone as potential early predictors in order to differentiate between infected pancreatic necrosis and sterile pancreatic necrosis in patients with acute pancreatitis. MATERIAL AND METHODS: Serum levels of CBG, total cortisol, calculated free cortisol, and plasma levels of adrenocorticotropic hormone were determined in 109 consecutive patients with acute pancreatitis. C-reactive protein was measured as the control parameter. Thirty-five patients developed necrotizing pancreatitis and 10 developed infection of the necrosis. Blood was monitored for 6 days after the onset of pain; 30 healthy individuals served as controls. RESULTS: Of all parameters only CBG showed a significant difference (p = 0.0318) in its peak levels measured in the first 48 h in patients with sterile (26.5 microg/ml, range 21.3-34.7) and infected (16.0 microg/ml, range 15.2-25.0) necrosis at a cut-off level of 16.8 microg/ml. That difference was further preserved for the first 6 days after onset of pain. CONCLUSIONS: In our group of patients, a decreased CBG level below 16.8 g/ml within the initial 48 h of acute pancreatitis was an early predictor of later infected pancreatic necrosis, with a positive predictive value of 100% and a negative predictive value of 87.5%.     

Prophylactic antibiotic treatment in acute necrotizing pancreatitis: Results from a meta-analysis

Objective. The effect of prophylactic antibiotic treatment on infection and survival of acute necrotizing pancreatitis (ANP) remains uncertain. The aim of this study was to assess the long-term efficacy of prophylactic antibiotic treatment for ANP. Material and methods. Searches were carried out of electronic databases including Medline, EMBASE, the Cochrane Controlled Trials Register, the Science Citation Index, and PubMed (updated to December 2007), and manual bibliographical searches were also conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing prophylactic antibiotic treatment with placebo or no treatment was performed. Results. Eight RCTs including 540 patients were assessed. The outcomes included infected necrosis, death, non-pancreatic infection, surgical intervention, and length of hospital stay. Prophylactic antibiotic use leads to a significant reduction of infected necrosis (relative risk (RR) 0.69, 95% CI, 0.50–0.95; p=0.02), non-pancreatic infections (RR 0.66 95% CI, 0.48–0.91; p=0.01), and length of hospital stay (p=0.004) but was not associated with a statistically significant reduction in mortality (RR 0.76 95% CI, 0.50–1.18; p=0.22) and surgical intervention (RR 0.90 95% CI, 0.66–1.23; p=0.52). In a subgroup analysis, carbapenem was associated with a significant reduction in infected necrosis (p=0.009) and non-pancreatic infections (p=0.006), whereas other antibiotics were not. Conclusions. Prophylactic antibiotic treatment is associated with a significant reduction of pancreatic or peripancreatic infection, non-pancreatic infection, and length of hospital stay, but cannot prevent death and surgical intervention in acute necrotizing pancreatitis.     

Profile of and risk factors for early unplanned readmissions in patients with acute necrotizing pancreatitis

IntroductionAcute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population.MethodsWe performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients.ResultsOne hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5–17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission.ConclusionPatients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.     

预防性使用抗生素对急性坏死性胰腺炎治疗作用的Meta分析

目的:评价预防性使用抗生素对治疗急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)的作用.方法:在Medline、PubMed、Springer、Ovid、Elsevier、Embase、CNKI、维普数据库中,检索1994-01/2011-10发表的文献.按入选标准,最终纳入5篇文献,使用RevMan5.1进行统计分析.结果:预防性使用抗生素治疗急性坏死性胰腺炎与对照组相比,并不能显著改善生存率(RR0.75,95%CI0.43-1.28,P=0.29),也不能降低胰腺感染(RR0.81,95%CI0.55-1.19,P=0.29)、胰外感染(RR0.79,95%CI0.59-1.06,P=0.12)及手术干预(RR0.78,95%CI0.45-1.36,P=0.37)等并发症的发生几率.结论:对于预防性使用抗生素治疗急性坏死性胰腺炎,根据现有的随机对照治疗尚不能说明其可以显著降低病死率和减少并发症的发生.     

急性坏死性胰腺炎时肺部损伤发病机制的研究

目的探讨急性坏死性胰腺炎（ＡＮＰ）对肺损伤影响的作用机制。方法用３．５％牛磺胆酸经胰胆管逆行注射建立ＡＮＰ模型，观察血清炎性细胞因子和介质的变化及肺损伤的病理改变。结果ＡＮＰ可引起炎性细胞因子ＩＬ－１β、ＩＬ－６，ＴＮＦα和炎性介质ＰＬＡ２、淀粉酶升高，也可引起血中和肺组织内ＴＮＦα，ＩＬ－１β的过度表达及肺部严重受损。用生长抑素治疗后，炎性细胞因子和介质明显下降和肺组织受损减轻。结论ＡＮＰ造成肺损伤与炎性细胞因子过度释放和参与有关。     

JAM-C在小鼠急性坏死性胰腺炎模型不同组织中的表达

目的:研究连接黏附分子C(JAM-C)在小鼠急性坏死性胰腺炎(ANP)模型胰腺、肾脏和肺脏组织中的表达.方法:采用雨蛙素和脂多糖联合腹腔注射的方法建立小鼠ANP模型.模型组(ANP组)小鼠腹腔内注射雨蛙素(50 μg/kg),连续6次,每次间隔1 h,在末次注射雨蛙素后,即向小鼠腹腔内注射脂多糖(LPS)(10 mg/kg);对照组小鼠腹腔内注射等体积生理盐水.在末次注射3 h后,用眼球取血法收集血液,检测血清淀粉酶,并取胰腺、肾脏、肺脏组织,通过Western blot印迹杂交法检测JAM-C在这些组织上的表达.结果:JAM-C在ANP组的胰腺、肺脏和肾脏上均有着高表达,大于生理盐水对照组3倍以上(0.608±0.133 vs 0.176±0.024,0.718± 0.148 vs 0.160±0.027,0.654±0.085 vs 0.166±0.039,均P<0.05).结论:在小鼠ANP模型中,JAM-C在胰腺、肾脏和肺脏上的表达均明显增高,提示JAM-C在ANP发病过程中起到重要的作用.     

Factors and outcomes associated with pancreatic duct disruption in patients with acute necrotizing pancreatitis

Background and aimsAcute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP.MethodsThis retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption.ResultsMPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%).ConclusionsMPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items.     

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

INTRODUCTION Acute pancreatitis (AP) is often complicated by intestinal injury. However, its pathogenesis remains unclear. As we know, AP involves a complex array of mediators initiating and amplifying the systemic inflammatory response and therefore lead…     

Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis

ObjectivesTo investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.MethodsSterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10⁸ CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS.ResultsMoxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10⁷ ± 2.4·10⁷ vs. AN 4.9·10⁴ ± 2.6·10⁴ CFU/g; p < 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p < 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p < 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p < 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis.ConclusionIn the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.     

硫氧还蛋白-1在急性坏死性胰腺炎大鼠肺组织中的表达及褪黑素干预的影响

目的:探讨内源性硫氧还蛋白-1(Trx-1)在急性坏死性胰腺炎(ANP)大鼠模型肺组织中的表达:观察褪黑素对ANP胰和肺脏的保护作用和对肺组织Trx-1表达的影响.方法:将72只SD大鼠随机分成对照组(C组,n=24)、急性胰腺炎组(A组,n=24)、褪黑素前干预组(M组,n=24).A组用6%的左旋精氨酸(L-Arginine,L-Arg)腹腔内注射,每次25 mL/kg体质量,共3次,注射间隔1 h,诱导ANP模型,在首次注射L-Arg前30 min腹腔注射生理盐水20mL/kg体质量1次;C组同法注射相当于A组各次注射用量的等容积生理盐水:M组在诱导胰腺炎前30 min腹腔内注射0.25%褪黑素(20mL/kg体质量)干预.在注射完L-Arg后的6、12、24 h三个时点分批处死大鼠.应用免疫组织化学技术检测各组ANP肺组织Trx-1的表达.并观察各组对应各时点胰腺、肺组织病理学和肺免疫组织化学的改变;抽取动脉血测定Trx-1和淀粉酶.结果:A组大鼠胰腺和肺组织病理损伤在6、12、24 h时点比C组明显加重(均P＜0.01);M组胰腺和肺组织病理损伤在6、12、24 h时点较A组明显减轻(P＜0.01或0.05).A组、M组肺组织表达Trx.1量在6、12、24 h时点较C组显著升高(均P<0.01).在24 h,A组血清淀粉酶较C组显著升高(4 598 U/L±2 274 U/L vs2 033U/L±863 U/L,P＜0.01);M组较A组低(3 990U/L±1 146 U/L vs 4 598 U/L±2 274 U/L,P＜0.05).A组大鼠血清Trx-1含量在6、12 h时点显著降低,24 h时点显著升高,呈前低后高趋势;与A组比较,M组血清Trx-1在6、12 h时点显著升高,24 h时点显著降低,量的峰值前移.结论:Trx-1在ANP肺损伤组织中的过度表达与急性胰腺炎相关性肺损伤关系密切.褪黑素影响Trx-1表达,并可能在一定程度上减轻ANP的胰、肺组织损伤.     

抗氧化剂对急性坏死性胰腺炎大鼠一氧化氮、丙二醛的影响

目的　探讨抗氧化剂N_乙酰半胱氨酸 (NAC)对急性坏死性胰腺炎 (ANP)大鼠胰腺组织一氧化氮 (NO)及丙二醛(MDA)的影响。方法　雄性SD大鼠 114只 ,随机分成正常对照组 (C组 ,n =3 0 )、急性胰腺炎组 (A组 ,n =42 )和NAC干预组 (N组 ,n= 42 )。A组分 2次腹腔内注射 8%L_精氨酸 (L_Arg) 1 2mg/g诱导ANP ;C组同法腹腔内注射等量生理盐水 ;N组先提前 1小时 (h)腹腔内注射 0 5mol/L的NAC 0 0 5mg/g ,然后同A组方法诱导ANP。在首次注射L_Arg后于 6h、12h、2 4h、3 6h、48h、72h分批处死大鼠 ,观察大鼠胰腺组织NO和MDA水平及胰腺病理变化。结果　N组各时点NO和MDA水平均较A组明显降低 (均P <0 0 1或P<0 0 5) ,N组 12h、2 4h、3 6h、48h、72h的胰腺病理改变较A组的明显减轻 (均P <0 0 1或P <0 0 5)。结论　NAC可降低胰腺组织NO、MAD水平 ,减轻了实验性ANP大鼠的胰腺损害 ,对胰腺组织有保护作用     

Effect of antibiotic prophylaxis on acute necrotizing pancreatitis: Results of a randomized controlled trial

Background and Aims: This study addresses whether antibiotic prophylaxis is beneficial for acute necrotizing pancreatitis. Methods: This randomized, controlled trial enrolled 276 patients with severe acute pancreatitis. There were 56 patients with 30% or more necrosis proved by contrast‐enhanced computerized tomography who were eligible for randomization: 29 in the study group and 27 in the control group, who received i.v. imipenem–cilastatin (3 × 500 mg/day) within 72 h of the onset of symptoms for 7–14 days, and no antibiotic prophylaxis, respectively. The primary end‐point was the incidence of infectious complication. The secondary end‐points were mortality, the incidence of necrosectomy for infected necrosis, the incidence of organ complication and hospital courses. Results: Characteristics of baseline data were similar in the two groups. No significant differences were found in the incidence of infected pancreatic necrosis (37% vs 27.6%), mortality (10.3% vs 14.8%) and the incidence of operative necrosectomy (29.6% vs 34.6%) between the study group and the control group (P > 0.05). The incidence of extrapancreatic infections, organ complications and hospital courses between the groups were also not significantly different. However, a significantly increased incidence of fungal infection was observed in the study group versus the control group (36.1% vs 14.2%, P < 0.05). Conclusion: There was no benefit in the outcomes when antibiotic prophylaxis was routinely used in patients with acute necrotizing pancreatitis.     

JAM-C单抗对小鼠急性坏死性胰腺炎的抑制作用

目的:观察JAM-C单克隆抗体对小鼠急性坏死性胰腺炎(ANP)模型胰腺和全身炎症的抑制作用.方法:采用雨蛙素和脂多糖联合腹腔注射的方法建立小鼠重症急性胰腺炎模型.生理盐水对照组(NS组):小鼠给予腹腔注射无菌生理盐水(10 mL/kg),共注射6次,间隔1 h;ANP模型组(ANP组):小鼠给予腹腔注射雨蛙素(50μg...     

乌司他丁、大黄对急性胰腺炎大鼠联合治疗效果分析

目的 通过采用乌司他丁与生大黄联合治疗急性胰腺炎大鼠动物模型，寻找治疗急性胰腺炎更好的治疗方法。方法 先建立急性胰腺炎大鼠模型，然后分为四组，分别测定每组血清液粉酶(AMS)肿瘤坏死因子(TNFα)及胰腺标本染色及大概生存时间。结果 A、B、C、D组TNFα、AMS含量及胰腺病理改变呈A，B，C，D，而生存时间显著不同。结论 乌司他丁、大黄联合治疗急性坏死性胰腺炎大鼠效果比单一效果更佳。     

大承气汤对急性坏死性胰腺炎大鼠胰腺水通道蛋白1的影响

目的 观察急性坏死性胰腺炎( ANP)大鼠胰腺组织水通道蛋白1(AQP1)的表达以及大承气汤对其的影响.方法 160只雄性SD大鼠按随机数字法分为对照组、ANP组、地塞米松组、乙酰唑胺组及大承气汤组,每组32只.采用胆胰管逆行注射5％牛磺胆酸钠方法制备ANP模型.地塞米松组于造模后即刻静脉给予地塞米松4 mg/kg体重;乙酰唑胺组于造模前2h用含乙酰唑胺的生理盐水1ml灌胃;大承气汤组于造模前48、24、2h分别用大承气汤2ml/次灌胃;对照组仅开腹触摸胰腺数次后关腹.制模后3、6、12、18 h分批处死8只大鼠.记录腹水量;检测血清淀粉酶;胰腺组织病理检查及电镜观察;伊文思兰(EB)血管外渗法检测毛细血管通透性;实时PCR和蛋白质印迹法检测AQP1 mRNA和蛋白表达.结果 ANP组血清淀粉酶水平显著升高,胰腺损伤明显;地塞米松组和大承气汤组淀粉酶水平较ANP组降低,胰腺损伤减轻;乙酰唑胺组淀粉酶水平高于ANP组,胰腺病理损伤较ANP组加重.造模后6h,对照组、ANP组、地塞米松组、乙酰唑胺组、大承气汤组胰腺组织EB含量分别为(13.44±2.56)、( 126.35±14.80)、(86.31±14.46)、(108.99±15.07)、(78.29±16.85) mg/L;AQP1 mRNA表达量为(170.07±22.48)％、(83.93±8.98)％、(117.09±10.70)％、(69.00±8.98)％、(112.82±11.79)％;AQP1蛋白表达量为0.23±0.06、0.10±0.02、0.32±0.03、0.13±0.02、0.45±0.04.ANP组的EB量显著高于对照组,而AQP1mRNA及蛋白的表达显著低于对照组(P值均＜0.05);地塞米松组及大承气汤组EB含量显著低于ANP组,而AQP1 mRNA及蛋白的表达显著高于ANP组(P值均＜0.05).结论 AQP1在ANP大鼠胰腺组织毛细血管渗漏的发生中起重要作用.大承气汤通过调控AQP1的表达可减轻ANP大鼠的胰腺损伤.     

Toll样受体4在猪急性坏死性胰腺炎肠道组织中的表达及其意义

目的:探讨猪急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)回肠组织中Toll样受体4(Toll-like receptor4,TLR4)的表达及其意义.方法:选择太湖梅山猪,随机分成对照组(C,n=4)、急性坏死性胰腺炎组(ANP,n=4).诱导制备ANP模型.用分光光度法检测血清及回肠组织匀浆中二胺氧化酶(DAO)活性;动态比浊法检测血浆内毒素水平;RT-PCR检测回肠黏膜组织TLR4、TNF-α及IL-6mRNA表达.结果:ANP组回肠组织DAO水平明显低于C组,血清中DAO明显升高(P<0.05).ANP组血浆内毒素水平较C组明显升高(P<0.05);回肠黏膜组织TLR4、TNF-α、IL-6mRNA在C组表达非常低,ANP组表达明显增加;TLR4mRNA表达水平与肠黏膜DAO水平呈负相关(r=-0.762,P=0.028),与血浆内毒素呈正相关(r=0.778,P=0.023).结论:ANP时回肠组织内TLR4mRNA表达上调,可能与ANP肠黏膜屏障功能障碍有关;其可能机制与TLR4介导激活核转录因子NF-αB信号转导途径有关.     

Erythropoietin: a possible cytoprotective cytokine in acute necrotizing pancreatitis

Background/purpose

Despite decades of research and clinical trials, a specific therapeutic treatment for acute pancreatitis (AP) has yet to be developed. The aim of the present study was to investigate the effects of erythropoietin on the severity of taurocolic acid-induced acute necrotizing pancreatitis.

Methods

Forty-seven male Wistar albino rats were randomized into seven experimental groups. In group I, animals were sham-operated (n = 5). In groups II, III, IV, IIepo, IIIepo, and IVepo, AP was induced by sodium taurodeoxycholate treatment (n = 7). In groups II, III, and IV, 1 ml normal saline and in groups IIepo, IIIepo, and IVepo, 1000 U/kg body weight erythropoietin (EPO) was administered intramuscularly immediately after the induction of AP. Animals were killed at 24, 48, and 72 h postoperatively. Histopathological and biochemical evaluations were performed.

Results

The serum levels of interleukin-6 (IL-6) and tissue levels of malondialdehyde were found to be significantly lower in EPO-administered groups when compared with the levels in groups without EPO treatment. The severity of pancreatic edema, acinar necrosis, inflammation, and perivascular infiltrate were reduced in all the EPO groups compared with the no-treatment groups.

Conclusions

Our findings may reflect the possible cytoprotective effect of EPO in acute necrotizing pancreatitis.     

奥曲肽治疗急性坏死性胰腺炎作用机制的实验研究

目的 探讨奥曲肽治疗急性坏死性胰腺炎（ＡＮＰ）的作用机制。方法 作者采用核素示踪和放射自显影技术,研究了奥曲肽对正常大鼠和大鼠ＡＮＰ时胰腺泡细胞氨基酸摄取、酶蛋白合成及分泌功能的影响。结果 奥曲肽对正常胰腺腺泡细胞和呈点同血坏死的ＡＶＰ胰腺腺细胞氨基酸摄取、酶蛋白合成均无明显影响,但可明显抑制胰腺腺胞细胞的外作泌功能,导致细胞内酶原颗粒积聚,ＡＮＰ时胰腺腺泡细胞出现底膜及侧膜异位分泌,奥曲肽能够减